Infertility in adult female rats, exposed neonatally to any of a large variety of agents, including gonadal steroid hormones, is well known. These animals are anovulatory and fail to undergo estrous cycles. Many studies have been directed at the changes in the central nervous system, and particularly at the mechanism controlling anterior pituitary gonadotropins, in attempting to understand the induced sterility. However, treatments which have produced ovulation of normal ova, matings with fertile males, fertilization of oviductal ova, and maintenance of functional corpora lutea have not resulted in successful pregnancies. Implantation of blastocysts and decidualization of the uterine endometrium generally have not been successful; i.e. the animals suffer from uterine infertility. In the present proposal experiments are outlined which will examine whether this aspect of their infertility is due to a direct effect of the early steroid exposure upon the uterus, to the subsequent lack of cyclic ovarian function, or to both. Neonatal female rats treated on day 5 postpartum with various doses of testosterone propionate or estradiol benzoate, will be studied at puberty, or after 30 or 60 days of acyclic ovarian function. The uterine responses, after ovariectomy, to exogenous steroid hormones will be compared to those of controls treated neonatally with oil or with controls which have been ovariectomized and implanted with estradiol-containing silastic tubing. The responses to be studied include; the growth stimulating effect of estradiol, changes in uterine histamine and prostaglandin content, as well as in the enzymes which control prostaglandin synthesis (phospholipase A2 and cyclooxygenase), decidual formation following uterine trauma in animals treated with progesterone plus estrogen and uterine implantation rate of blastocysts transferred from normal females. These responses will also be examined in females which have had their ovaries removed from 30 to 60 days to determine the possible recovery from uterine infertility. The results will contribute to our understanding of the role that the uterus plays in infertility and aid in the formulation of corrective therapy.